Abstract
Abstract The earliest transitional (T1) B cells are significantly more sensitive to cell death than the late transitional (T2) and mature follicular (Fo) B cells and aberrant survival of T1 B cells can lead to autoimmune disease. While it is known that survival of splenic B cells is predominantly regulated by B cell antigen receptor (BCR) and B cell activation factor receptor (BAFF-R), the mechanisms by which these receptors mediate survival is less clear. We have investigated the developmental stage-specific regulation of anti-apoptotic genes and the transcription factor NF-κB, which is a major modulator of these genes. We found that in vivo, T1 B cells express the highest levels of Mcl-1 and Bcl-xL, whereas mature Fo B cells predominantly express Bcl-2. Consistent with T1 cell sensitivity to cell death following BCR crosslinking, T1 B cells only weakly induced the expression of anti-apoptotic genes (Mcl-1 and Bcl-xL) relative to robust induction in T2 and mature Fo B cells following BCR stimulation. BCR-induced expression of NF-κB (NF-κB1, RelA, cRel, NF-κB2 and RelB) coincides with that of anti-apoptotic genes; lowest in T1 and highest in mature Fo B cells. These findings suggest that T2 and mature Fo B cell survival may be linked to sustained expression of NF-κB and anti-apoptotic genes. This study is supported by NIH RO1 A1060729
Published Version
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